The long-range objectives of this research proposal are to study the roles of growth hormone (GH) and GH-induced somatomedin (SM), or non-suppressible insulin-like activity (NSILA-S), in growth regulation and diabetes mellitus. To pursue these objectives, it is proposed that a radioligand assay be developed with adequate sensitivity and specificity to measure plasma levels of SM (or NSILA-S) under both physiological and pathological conditions. Plasma SM (or NSILA-S) levels will be measured in diabetic subjects to determine whether abnormalities exist under "physiological" conditions or in response to various provocative tests. In vivo animal studies are planned to determine the time-course of SM (or NSILA-S) induction following GH administration, the subsequent biochemical responses and cellular growth. We will examine the possible role of SM (or NSILA-S) in the feedback regulation or GH secretion through its action on the pituitary gland or indirectly via its effect either on the hypothalamic GH releasing factor or somatostatin.